This proposal focuses on development of technology that is suited for both ultra-high resolution animal imaging systems and other applications such as human breast and head imaging. An integral part of our work to date is the development of a highly modular approach to the detectors and supporting electronics. This approach assures that imaging resources built using the technology can easily adapt to the changing demands of the biological research. In the previous funding period we made considerable progress on our original goals of developing a single ended readout depth-of-interaction (DOI) detector design and the supporting electronics and event estimation algorithms. During that effort, we realized that Gieger-Muller Avalanche Photodiodes (GM-APD) offered an optimal readout scheme for our DOI approach. In this renewal application, we propose to further develop detector modules, electronics, and reconstruction algorithms to support a depth-of-interaction (DOI) detector design and supporting electronics (dMiCE). A major focus is on cost effective designs, and therefore our dMiCE module is based on a single- ended readout of light with light sharing between pairs of crystals to provide the DOI information. The overall goal is to achieve spatial resolutions < 1.0 mm with sensitivity in a typical small animal configuration of > 15%. The effort will include the development of maximum likelihood estimators for crystal-of-interaction and depth-of-interaction in segmented crystal module designs as well as better methods for optimization of our DOI approach implemented in field programmable gate arrays (FPGA) and application specific integrated circuits (ASIC). Another aspect of the work is to extend the DOI designs to investigate potential applications in time- of-flight (TOF) systems by utilizing DOI based TOF correction to improve the overall timing resolution of our detector/electronics designs. The net result of our work will be contributions to the general knowledge of options for detector and electronics design for high-resolution detector systems as well as insight into methods to optimize TOF performance for different detector module designs. This work is the foundation for new scanner designs to address biological research needs. PUBLIC HEALTH RELEVANCE: Imaging is increasingly being used for pre-clinical studies to improve the quality of data and decrease the time to acquire statistically significant data. This grant is developing new technologies to allow increasing the resolution and sensitivity of pre-clinical positron emission scanners. The technology can also be used to develop high resolution PET scanners specific to specific human clinical applications such as neurology. The detectors, electronics, and image reconstruction algorithms developed under this grant is yet another step in the advancement of medical imaging.